Issue

Vol. 13 (2021)

Zeptomole Imaging of Cytosolic MicroRNA Cancer Biomarkers with A Light-Controlled Nanoantenna

https://doi.org/10.1007/s40820-021-00732-1
Yang Song
School of Mechanical and Materials Engineering, Washington State University, Pullman, WA 99164, USA
Xiaoli Cai
School of Mechanical and Materials Engineering, Washington State University, Pullman, WA 99164, USA
Grayson Ostermeyer
School of Biological Sciences, Washington State University, Pullman, WA 99164, USA
Shichao Ding
School of Mechanical and Materials Engineering, Washington State University, Pullman, WA 99164, USA
Dan Du
School of Mechanical and Materials Engineering, Washington State University, Pullman, WA 99164, USA
Yuehe Lin
School of Mechanical and Materials Engineering, Washington State University, Pullman, WA 99164, USA

Corresponding Author: Yuehe Lin

yuehe.lin@wsu.edu

Nano-Micro Letters, Vol. 13 (2021), Article Number: 213

Abstract

Detecting and quantifying intracellular microRNAs (miRNAs) are a critical step in resolving a cancer diagnostic and resolving the ensemble of gene products that orchestrate the living state of cells. However, the nanoprobe for detecting low abundance miRNAs in cell cytosol is restricted by either the “one-to-one” signal-trigger model or difficulty for cytosol delivery. To address these challenges, we designed a light-harvesting nanoantenna-based nanoprobe, which directs excitation energy to a single molecule to sensitively detect cytosolic miRNA. With light irradiation, the light-harvesting nanoantenna effectively disrupted lysosomal structures by generation of reactive oxygen species, substantially achieved cytosol delivery. The nanoantenna containing > 4000 donor dyes can efficiently transfer excitation energy to one or two acceptors with 99% efficiency, leading to unprecedented signal amplification and biosensing sensitivity. The designed nanoantenna can quantify cytosolic miR-210 at zeptomolar level. The fluorescence lifetime of the donor exhibited good relationship with miR-210 concentration in the range of 0.032 to 2.97 amol/ngRNA. The zeptomole sensitivity of nanoantenna provides accurate bioimaging of miR-210 both in multiple cell lines and in vivo assay, which creates a pathway for the creation of miRNA toolbox for quantitative epigenetics and personalized medicine.


Highlights:


1 Based on førster resonance energy transfer, the nanoantenna containing over 4000 donor dyes can achieve unprecedented signal amplification and biosensing sensitivity.
2 With light irradiation, the light-harvesting nanoantenna effectively disrupted lysosomal structures by generation of reactive oxygen species, substantially achieved cytosol delivery.
3 The zeptomolar sensitivity of nanoantenna provides accurate bioimaging of miR-210 in multiple cell lines and in vivo assay, which creates a pathway for the creation of miRNA toolbox for quantitative epigenetics and personalized medicine.

Keywords

Light-harvest Nanoantenna miRNA detection Zeptomole Multiple cell lines
Song, Yang, Xiaoli Cai, Grayson Ostermeyer, Shichao Ding, Dan Du, and Yuehe Lin. 2021. “Zeptomole Imaging of Cytosolic MicroRNA Cancer Biomarkers With A Light-Controlled Nanoantenna”. Nano-Micro Letters 13 (October):213. https://doi.org/10.1007/s40820-021-00732-1.
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References
  1. H. Dong, X. Meng, W. Dai, Y. Cao, H. Lu et al., Highly sensitive and selective microRNA detection based on DNA-bio-bar-code and enzyme-assisted strand cycle exponential signal amplification. Anal. Chem. 87, 4334–4340 (2015). https://doi.org/10.1021/acs.analchem.5b00029
  2. W. Filipowicz, S.N. Bhattacharyya, N. Sonenberg, Mechanisms of Post-transcriptional regulation by microRNAs: are the answers in sight? Nat. Rev. Genet 9, 102–114 (2008). https://doi.org/10.1038/nrg2290
  3. W. Lu, Y. Chen, Z. Liu, W. Tang, Q. Feng et al., Quantitative detection of microRNA in one step via next generation magnetic relaxation switch sensing. ACS Nano 10, 6685–6692 (2016). https://doi.org/10.1021/acsnano.6b01903
  4. Z. Zhao, H. Fan, G. Zhou, H. Bai, H. Liang et al., Activatable fluorescence/MRI bimodal platform for tumor cell imaging via MnO2 nanosheet-aptamer nanoprobe. J. Am. Chem. Soc. 136, 11220–11223 (2014). https://doi.org/10.1021/ja5029364
  5. X.A. Liu, R. Freeman, R. Yehezkeli, O. Willner, Multiplexed aptasensors and amplified DNA sensors using functionalized graphene oxide: application for logic gate operations. ACS Nano 6, 3553–3563 (2012). https://doi.org/10.1021/nn300598q
  6. X. Zhao, L. Xu, M. Sun, W. Ma, X. Wu et al., Gold-quantum dot core-satellite assemblies for lighting up microRNA in vitro and in vivo. Small 12, 4662–4668 (2016). https://doi.org/10.1002/smll.201503629
  7. W. Ma, P. Fu, M. Sun, L. Xu, H. Kuang et al., Dual quantification of microRNAs and telomerase in living cells. J. Am. Chem. Soc. 139, 11752–11759 (2017). https://doi.org/10.1021/jacs.7b03617
  8. S. Li, L. Xu, M. Sun, X. Wu, L. Liu et al., Hybrid nanoparticle pyramids for intracellular dual microRNAs biosensing and bioimaging. Adv. Mater. 29, 1606086 (2017). https://doi.org/10.1002/adma.201606086
  9. W. Ma, M. Sun, P. Fu, S. Li, L. Xu et al., A chiral-nanoassemblies-enabled strategy for simultaneously profiling surface glycoprotein and microRNA in living cells. Adv. Mater. 29, 1703410 (2017). https://doi.org/10.1002/adma.201703410
  10. W. Xia, J. Li, L. Chen, B. Huang, S. Li et al., MicroRNA-200b regulates cyclin d1 expression and promotes s-phase entry by targeting RND3 in hela cells. Mol. Cell. Biochem. 344, 261–266 (2010). https://doi.org/10.1007/s11010-010-0550-2
  11. Y. Zhang, B. Zheng, C. Zhu, X. Zhang, C. Tan et al., Single-layer transition metal dichalcogenide nanosheet-based nanosensors for rapid, sensitive, and multiplexed detection of DNA. Adv. Mater. 27, 935–939 (2015). https://doi.org/10.1002/adma.201404568
  12. Y. Yuan, R. Li, Z. Liu, Establishing water-soluble layered WS2 nanosheet as a platform for biosensing. Anal. Chem. 86, 3610–3615 (2014). https://doi.org/10.1021/ac5002096
  13. Y. Song, X. Yan, G. Ostermeyer, S. Li, L. Qu et al., Direct cytosolic microRNA detection using single-layer perfluorinated tungsten diselenide nanoplatform. Anal. Chem. 90, 10369–10376 (2018). https://doi.org/10.1021/ac5002096
  14. K. Trofymchuk, A. Reisch, P. Didier, F. Fras, P. Gilliot et al., Giant light-harvesting nanoantenna for singlemolecule detection in ambient light. Nat. Photonics 3, 654–657 (2009). https://doi.org/10.1038/s41566-017-0001-7
  15. N. Melnychuk, A.S. Klymchenko, DNA-functionalized dye-loaded polymeric nanoparticles: ultrabright FRET platform for amplified detection of nucleic acids. J. Am. Chem. Soc. 140, 10856–10865 (2018). https://doi.org/10.1021/jacs.8b05840
  16. N. Melnychuk, S. Egloff, A. Runser, A. Reisch, A.S. Klymchenko, Light-harvesting nanoparticle probes for fret-based detection of oligonucleotides with single-molecule sensitivity. Angew. Chem. Int. Ed. 59, 6811–6818 (2020). https://doi.org/10.1002/anie.201913804
  17. Y. Yang, J. Huang, X. Yang, K. Quan, H. Wang et al., Aptazyme-gold nanoparticle sensor for amplified molecular probing in living cells. Anal. Chem. 88, 5981–5987 (2016). https://doi.org/10.1021/acs.analchem.6b00999
  18. J. Li, J. Wang, S. Liu, N. Xie, K. Quan et al., Amplified FRET nanoflares: an endogenous mrna-powered nanomachine for intracellular microRNA imaging. Angew. Chem. Int. Ed. 59, 20104–20111 (2020). https://doi.org/10.1002/anie.202008245
  19. H. Peng, X.F. Li, H. Zhang, X.C. Le, A microRNA-initiated DNAzyme motor operating in living cells. Nat. Commun. 8, 14378 (2017). https://doi.org/10.1038/ncomms14378
  20. X. Zhang, Y. Xiao, X. Qian, A ratiometric fluorescent probe based on FRET for imaging Hg2+ ions in living cells. Angew. Chem. Int. Ed. 47, 8025–8029 (2008). https://doi.org/10.1016/j.snb.2016.09.177
  21. X. Li, X. Gao, W. Shi, H. Ma, Design strategies for water-soluble small molecular chromogenic and fluorogenic probes. Chem. Rev. 114, 590–659 (2014). https://doi.org/10.1021/cr300508p
  22. J. Chan, S.C. Dodani, C.J. Chang, Reaction-based small-molecule fluorescent probes for chemoselective bioimaging. Nat. Chem. 4, 973–984 (2012). https://doi.org/10.1038/nchem.1500
  23. S. Egloff, N. Melnychuk, A. Reisch, S. Martin, A.S. Klymchenko, Enzyme-free amplified detection of cellular microRNA by light-harvesting fluorescent nanoparticle probes. Biosens. Bioelectron. 179, 113084 (2021). https://doi.org/10.1016/j.bios.2021.113084
  24. C. Chen, D.A. Ridzon, A.J. Broomer, Z. Zhou, D.H. Lee et al., Real-time quantification of microRNAs by stem-loop RT-PCR. Nucl. Acids Res. 33, e179 (2005). https://doi.org/10.1093/nar/gni178
  25. R.W. Carthew, E.J. Sontheimer, Origins and mechanisms of miRNAs and siRNAs. Cell 136, 642–655 (2009). https://doi.org/10.1016/j.cell.2009.01.035
  26. L. Nuhn, S. Van Herck, A. Best, K. Deswarte, M. Kokkinopoulou et al., FRET monitoring of intracellular ketal hydrolysis in synthetic nanoparticles. Angew. Chem. Int. Ed. 57, 10760–10764 (2018). https://doi.org/10.1002/anie.201803847
  27. Y. Liu, G. Yang, S. Jin, R. Zhang, P. Chen et al., J-Aggregate-based FRET monitoring of drug release from polymer nanoparticles with high drug loading. Angew. Chem. Int. Ed. 59, 20065–20074 (2020). https://doi.org/10.1002/anie.202008018
  28. B. Rathore, K. Sunwoo, P. Jangili, J. Kim, J.H. Kim et al., Nanomaterial designing strategies related to cell lysosome and their biomedical applications: a review. Biomaterials 211, 25–47 (2019). https://doi.org/10.1016/j.biomaterials.2019.05.002
  29. J. Chen, J. Li, J. Zhou, Z. Lin, F. Cavalieri et al., Metal-phenolic coatings as a platform to trigger endosomal escape of nanoparticles. ACS Nano 13, 11653–11664 (2019). https://doi.org/10.1021/acsnano.9b05521
  30. P.K. Selbo, A. Weyergang, A. Høgset, O.J. Norum, M.B. Berstad et al., Photochemical internalization provides time- and space-controlled endolysosomal escape of therapeutic molecules. J. Controll. Release 148, 2–12 (2010). https://doi.org/10.1016/j.jconrel.2010.06.008
  31. K. Berg, M. Folini, L. Prasmickaite, P.K. Selbo, A. Bonsted et al., Photochemical internalization: a new tool for drug delivery. Curr. Pharm. Biotechnol. 8, 362–372 (2007). https://doi.org/10.2174/138920107783018354
  32. A. Qu, M. Sun, L. Xu, C. Hao, X. Wu et al., Quantitative zeptomolar imaging of miRNA cancer markers with nanoparticle assemblies. Proc. Natl. Acad. Sci. USA 116, 3391–3400 (2019). https://doi.org/10.1073/pnas.1810764116
  33. L. Ji, Y. Sang, G. Ouyang, D. Yang, P. Duan et al., Cooperative chirality and sequential energy transfer in a supramolecular light-harvesting nanotube. Angew. Chem. Int. Ed. 58, 844–848 (2019). https://doi.org/10.1002/anie.201812642
  34. P.Z. Chen, Y.X. Weng, L.Y. Niu, Y.Z. Chen, L.Z. Wu et al., Light-harvesting systems based on organic nanocrystals to mimic chlorosomes. Angew. Chem. Int. Ed. 55, 2759–2763 (2016). https://doi.org/10.1002/anie.201510503
  35. X.M. Chen, Q. Cao, H.K. Bisoyi, M. Wang, H. Yang et al., An efficient near-infrared emissive artificial supramolecular light-harvesting system for imaging in the golgi apparatus. Angew. Chem. Int. Ed. 59, 10493–10497 (2020). https://doi.org/10.1002/anie.202003427
  36. Z. Wu, M. Liu, Z. Liu, Y. Tian, Real-time imaging and simultaneous quantification of mitochondrial h2o2 and atp in neurons with a single two-photon fluorescence-lifetime-based probe. J. Am. Chem. Soc. 142, 7532–7541 (2020). https://doi.org/10.1021/jacs.0c00771
  37. L. Ge, Y. Tian, Fluorescence lifetime imaging of p-tau protein in single neuron with a highly selective fluorescent probe. Anal. Chem. 91, 3294–3301 (2019). https://doi.org/10.1021/acs.analchem.8b03992
  38. K. Zhou, H.K. Bisoyi, J.Q. Jin, C.L. Yuan, Z. Liu et al., Light-driven reversible transformation between self-organized simple cubic lattice and helical superstructure enabled by a molecular switch functionalized nanocage. Adv. Mater. 30, e1800237 (2018). https://doi.org/10.1002/adma.201800237
  39. Y.X. Zhu, H.R. Jia, G.Y. Pan, N.W. Ulrich, Z. Chen et al., Development of a light-controlled nanoplatform for direct nuclear delivery of molecular and nanoscale materials. J. Am. Chem. Soc. 140, 4062–4070 (2018). https://doi.org/10.1021/jacs.7b13672
  40. K.Y. Pu, K. Li, B. Liu, Cationic oligofluorene-substituted polyhedral oligomeric silsesquioxane as light-harvesting unimolecular nanoparticle for fluorescence amplification in cellular imaging. Adv. Mater. 22, 643–646 (2010). https://doi.org/10.1002/adma.200902409
  41. Y. Huang, J. Xing, Q. Gong, L.C. Chen, G. Liu et al., Reducing aggregation caused quenching effect through co-assembly of PAH chromophores and molecular barriers. Nat. Commun. 10, 169 (2019). https://doi.org/10.1038/s41467-018-08092-y
  42. M.H. Moros, B. Garet, E. Dias, J.T. Sáez, B. Grazú et al., Monosaccharides versus PEG functionalized NPs: influence in the cellular uptake. ACS Nano 6, 1565–1577 (2012). https://doi.org/10.1021/nn204543c
  43. N. Cheng, Y. Song, Q.Q. Fu, D. Du, Y.B. Luo et al., Aptasensor based on fluorophore-quencher nano-pair and smartphone spectrum reader for on-site quantification of multi-pesticides. Biosens. Bioelectron. 117, 75–83 (2018). https://doi.org/10.1016/j.bios.2018.06.002
  44. X. Huang, L. Ding, K.L. Bennewith, R.T. Tong, S.M. Welford et al., Hypoxia-inducible MIR-210 regulates normoxic gene expression involved in tumor initiation. Mol. Cell 35, 856–867 (2009). https://doi.org/10.1016/j.molcel.2009.09.006
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